By using carbophilic Lewis acids, In(OTf)3, NiCl2, and AuCl(PPh3)/AgNTf2, a concise and efficient synthesis of 1,3-disubstituted 1,2-dihydroisoquinolines has been achieved via tandem nucleophilic addition and cyclization of 2-(1-alkynyl)arylaldimines. Addition of proton sources such as water, CF3CH2OH, and 2,6-di-tert-butyl-4-methoxyphenol was essential for the Lewis acid-catalyzed tandem reactions with organometallic reagents. By switching these catalysts, various types of nucleophiles such as allylstannanes, silyl enol ethers, alkenylboronic acids, and active methylene compounds could be introduced at the C1 position of 1,2-dihydroisoquinolines in this transformation. Furthermore, this method proved to be applicable to the synthesis of 1H-isochromene derivatives via the same tandem reaction of 2-(1-alkynyl)arylaldehydes.

Multitasking catalyst: 1,2‐Dihydroisoquinoline derivatives are prepared in good yields by an In(OTf)3‐catalyzed tandem annulation reaction. The catalyst activates both the imine and alkyne to the addition of various nucleophiles and the subsequent intramolecular cyclization (see picture; OTf=trifluoromethanesulfonate).

Doppelkatalysator: Eine In(OTf)3‐katalysierte Tandemanellierung führt in hohen Ausbeuten zu 1,2‐Dihydroisochinolinen. Der Katalysator aktiviert die Imin‐ und die Alkingruppe für die Addition von Nucleophilen und anschließende intramolekulare Cyclisierung (siehe Schema; OTf=Trifluormethansulfonat).

arylaldehydes. -(OBIKA, S.; KONO, H.; YASUI, Y.; YANADA, R.; TAKEMOTO*, Y.; J. Org. Chem. 72 (2007) 12, 4462-4468; Grad. Sch. Pharm. Sci., Kyoto Univ., Sakyo, Kyoto 606, Japan; Eng.) -Jannicke 42-143